{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:06:10Z","timestamp":1793318770501,"version":"4.5.0"},"reference-count":46,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T00:00:00Z","timestamp":1727395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Pediatrics, University of Mississippi Medical Center"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: Perinatal infection is a major risk factor for diffuse white matter injury (dWMI), which remains the most common form of neurological disability among very preterm infants. The disease primarily targets oligodendrocytes (OL) lineage cells in the white matter but also involves injury and\/or dysmaturation of neurons of the gray matter. This study aimed to investigate whether neuroinflammation preferentially affects the cellular compositions of the white matter or gray matter. Method: Neuroinflammation was initiated by intracerebral administration of lipopolysaccharide (LPS) to rat pups at postnatal (P) day 5, and neurobiological and behavioral outcomes were assessed between P6 and P21. Results: LPS challenge rapidly activates microglia and astrocytes, which is associated with the inhibition of OL and neuron differentiation leading to myelination deficits. Specifically, neuroinflammation reduces the immature OLs but not progenitors and causes acute axonal injury (\u03b2-amyloid precursor protein immunopositivity) and impaired dendritic maturation (reduced MAP2+ neural fiber density) in the cortical area at P7. Neuroinflammation also reduces the expression of doublecortin in the hippocampus, suggesting compromise in neurogenesis. Utilizing a battery of behavioral assessments, we found that LPS-exposed animals exhibited deficits in sensorimotor, neuromuscular, and cognitive domains. Conclusion: Our overall results indicate that neuroinflammation alone in the early postnatal period can produce cardinal neuropathological features of dWMI.<\/jats:p>","DOI":"10.3390\/brainsci14100976","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T07:49:24Z","timestamp":1727423364000},"page":"976","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Early Postnatal Neuroinflammation Produces Key Features of Diffuse Brain White Matter Injury in Rats"],"prefix":"10.3390","volume":"14","author":[{"given":"John","family":"Waddell","sequence":"first","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuying","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, School of Health-Related Professionals, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Carter","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Truong","sequence":"additional","affiliation":[{"name":"Undergraduate Summer Research Program, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May","family":"Hebert","sequence":"additional","affiliation":[{"name":"Undergraduate Summer Research Program, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma","family":"Ojeda","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lir-Wan","family":"Fan","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhay","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0453-6921","authenticated-orcid":false,"given":"Yi","family":"Pang","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.clp.2018.05.007","article-title":"Public Health Implications of Very Preterm Birth","volume":"45","author":"Barfield","year":"2018","journal-title":"Clin. 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